Epithelium Derived Rclaxing Factor-Its Role in Airway Hyperreactivity-

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It is speculated that airway epithelium regulate airway tone by releasing epithelium derived relaxing factor (EpDRF). To examine this possibility, we tried to answer the following questions.1. Does EpDRF really exist? : By applying co-axial bioassay system developed by Ilhan and Sahin, we confirmed that guinea-pig airway epithelium releases smooth muscle relaxant factor. There was a criticism that the relaxation seen in this system is caused by tissue hypoxia due to the narrowing of tracheal lumen. We modified co-axial bioassay system to eliminate reduction of tracheal diameter by inserting steel coil inside. With this system, we observed relaxation of rabbit aortic strip when the epithelium intact trachea was stimulated with acetylcholine. From these results we concluded that relaxation seen in this system is not due to tissue hypoxia but due to the release of relaxing factor from tracheal epithelium. In addition, we examined effects of atropine, pirenzepine, and 4-DAMP on acetylcholi … More ne induced EpDRF release. Atropine and 4-DAMP were about 50 times more potent in suppressing relaxation than pirenzepine. From these results, we concluded that epithelial muscarinic-M3 receptor stimulation may be responsiblc in inducing the release of EpDRF.2. What is EpDRF? : We examined the possibility that nitric oxide is one of EpDRF in guinea-pig airways. We studied first, whether nitric oxide could relax isolated tracheal strips, and then examined the effects of known inhibitors of endothelium-dependent relaxation (EDR) in the vascular system, hemoglobin methylene blue, and N^G-monomethyl-L-arginine (L-NMMA), on epithelium-dependent relaxation (EpDR) induced by hyperosmotic stimuli in perfused whole tracheal preparations, Nitric oxide produced concentration-dependent and complete relaxation of epithelium-denuded tracheal strips. Preincubation of the whole trachea with hemoglobin significantly inhibited osmotic-induced EpDR, but preincubation with methylene blue and L-NMMA did not. Hemoglobin introduced into the epithelial side after EpDR induced by hyperosmotic stimuli reversed relaxation, but methylene blue and L-NMMA did not. These results suggest that although EpDR and vascular EDR have some pharmacological similarities and nitric oxide can relax airway smooth muscle, nitric oxide is not responsible for osmotic-induced EpDR. Less